Lack of oxygen rapidly leads to the demise of most animals. Menuz et al. (see the Perspective by Crowder) conducted a screen for mutants of the worm Caenorhabditis elegans that are particularly sensitive to the effects of anoxia. The gene Hyl-2, which encodes a ceramide synthase, is a member of a family of genes that influence life span in yeast. Worms have another gene, hyl-1, that also encodes a related ceramide synthase, whose mutants are instead more resistant to anoxia than normal animals. The two ceramide synthases have different specificities for fatty acyl chains, with HYL-2 preferentially producing ceramide molecules with shorter fatty acyl chains. Thus, the abundance of particular ceramides can influence cell survival mechanisms.